Cellular mechanisms of memory consolidation

虽然众所周知，海马体在学习和记忆中起着关键作用，但长期的陈述性记忆(例如，名字和面孔、关于世界的事实等)。被认为居住在新大脑皮层。因此，假设在海马体和新皮质之间的相互作用中发生了一些尚不清楚的过程，这些过程影响了突触输入对新皮质神经元的影响。这一过程依赖于海马体旁结构中的活动，例如来自海马体的信息必须通过的内嗅觉皮质和周围皮质。研究记忆巩固有几个困难，但很少有人提到的一个事实是，来自海马旁结构的与新皮质的连接主要针对第一层(以及第二/3层的一部分)。这导致对记忆巩固最重要的突触到达皮质锥体神经元的远端簇状树突，使得它们很难被检查。在这个项目中，我们的目标是使用我们实验室开发的一系列方法在体内和体外研究这些突触。我们将使用光遗传学工具来可视化和影响从内嗅觉皮质到簇状树突的突触输入。使用不同的树突记录方法(电生理和成像)，我们将检查这些输入对阈值下和阈值上活动的突触后影响。最后，我们将设计一项行为任务，在学习过程中和学习后调查完整动物的这些联系。

Although the hippocampus has long been known to play a key role in learning and memory, long-term declarative memories (e.g. names and faces, facts about the world, etc.) are thought to reside in neocortex. It is therefore assumed that some, as yet unknown, processes occur in the interaction between the hippocampus and the neocortex that affect the influence of synaptic inputs to neocortical neurons. This process depends on the activity in the parahippocampal structures such as the entorhinal and perirhinal cortices through which the information from the hippocampus must go. There are several difficulties in investigating memory consolidation but one that is not often mentioned is the fact that connections to the neocortex coming from the parahippocampal structures target predominantly layer 1 (and parts of layer 2/3). This has the consequence that synapses most likely to be important to memory consolidation arrive at the distal tuft dendrites of cortical pyramidal neurons making them very hard to examine.In this project, we aim to investigate these synapses in vivo and in vitro using a range of methodologies that have been developed in our laboratory. We will use optogenetic tools to visualize and influence synaptic input to tuft dendrites from the entorhinal cortex. Using various dendritic recording methods (electrophysiological and imaging) we will examine the postsynaptic influence of these inputs on subthreshold and suprathreshold activity. Lastly, we will design a behavioural task for investigating these connections in the intact animal during and after learning.